Analysis of the immunogenetic regluation of the T-macrophage interaction in both mice and men in continuing. The key aspects under analysis are the characterization of the target of T cell recognition, a complex of Ia antigen and immunogen, the genetic control of T cell activation by macrophages, analyzing the cellular sources of the Ir gene control and its relationship to genetic restrictions and the analysis of receptor function during T cell activation. Chimaeric mice of various types will be used to analyze the nature of genetic restrictions and Ir gene control. Rather than using only synthetic polypeptides in the analysis of Ir gene control, insulin is also being used as it is an antigen of clear-cut biological relevance. Antisera against receptors such as anti-idiotype sera will be used in attempts to analyze T cell receptor function.